| Written | 2008-11 | Philip L Lorenzi, Michael C Ryan, Ogechi N Ikediobi, John N Weinstein |
| | Laboratory of Molecular Pharmacology, National Institutes of Health, Bethesda, MD 20892, USA (PLL, MCR); University of California, San Francisco, San Francisco, CA, USA (ONI); M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA (JNW) |
| Description | ASNS is encoded on chromosome 7 and has 14 exons. The promoter begins 173 bases upstream of the start codon, which is on exon 4, with three GC-rich sequences (GC-I, GC-II, and GC-III) followed by two nutrient sensing response elements, NSRE-1 (ATGATGAAA; at nt -70) and NSRE-2 (GTTACA; at nt -49). The stop codon is on exon 14. |
| Transcription | The full length transcript (RefSeq variant 1; NM_133436 on Fig1) is 2348 bp long. Ten alternative splicing isoforms have been reported with most variation occurring primarily in the 5'UTR.
Various forms of cellular stress, including nutrient deprivation, lead to increased ASNS transcription. One component of that mechanism includes translation of the activating transcription factor family of proteins (ATF2, ATF3, ATF4, ATF5, and ATF6), all of which increase ASNS transcription through binding to NSRE-1 and/or NSRE-2. TRB3 is a negative feedback regulator of ATF4-dependent transcription, and C/EBP-beta is a negative regulator of ATF5-dependent transcription. DDIT3/CHOP is also a negative regulator of ASNS transcription.
ASNS has also been reported to be a significant target of transactivation by mutant p53, whereas wild-type p53 inhibits transcriptional activation of the NSREs.
ASNS mRNA has been shown to exhibit a half-life of 9 h and periodic, clock-like up-regulation every around 35 min in cell culture. |
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| | Representation of the ASNS gene, its mRNA splice variants, and its protein isoforms.
Each unique splice variant is identified by an accession number on the left-hand side. Exons are numbered at the top of the image. Lighter green indicates UTRs, and dark green indicates protein-coding regions. Exons are drawn to scale. Intronic sections are indicated by thin green lines and are not drawn to scale. |
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| Description | Transcripts NM_001673, NM_133436, NM_183356, BC008723, BC014621, BT007113, and M27396 encode a common 561 aa (64 kDa) ASNS protein sequence. Transcripts AK302189 and M15798 encode 540 aa N-terminally truncated proteins that differ in sequence between amino acids 312-322 and 332-339. Transcript AK302242 encodes a 478 aa isoform that is further truncated at the N-terminus. |
| Expression | Only the 561 aa isoform has been experimentally confirmed, and it has been found to be up-regulated by nutrient deprivation. Its half-life is reported to be 43-46 h. |
| Localisation | ASNS protein is cytoplasmic, but prediction algorithms also predict a small fraction of nuclear localization. |
| Function | ASNS catalyzes the synthesis of asparagine from glutamine and aspartic acid. In addition to providing asparagine for global protein synthesis, ASNS expression appears to be required for the transition from G1 to S phase of the cell cycle. |
| Homology | The 561 aa ASNS isoform has 29% identity with a protein called asparagine synthetase domain containing 1 (ASNSD1) that is 643 aa in length and encoded by a transcript (NM_019048) produced by chromosome 2. |
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